This is probably more simple and mundane than you had in mind, but I’d say a question that’s become harder to answer because of expanding knowledge is: What is the endocrine system?
We used to define it as a system of hormone-secreting glands, and illustrate it with a body figure showing the classic pituitary gland, pineal gland, thymus, thyroid gland, parathyroid glands, adrenal glands, and gonads, like this one from my own books. Such a figure is still useful, yet inadequate.
Research in the past several decades has now disclosed that every organ system in the body secretes hormones, so what does the term “endocrine system” mean anymore? See my latest attempt below the figure.